Ultrastructural changes in nodal and paranodal regions of myelinated mouse and rat optic nerve fibers were followed between 4 h and 28 days during the course of Wallerian degeneration. In the mouse, axoplasmic changes, including accumulation of organelles and segregation of microtubules, were detectable 4 h after transection, and progressed to a maximum level on day 4, at which time many axons were markedly swollen. Dense axoplasm was seen as early as 16 h and was a common feature of degenerating axoplasm at later times. Paranodal changes, which first appeared as early as 16 h after injury, included detachment of terminal loops of myelin from the axolemma, disconnection of terminal loops from compact myelin lamellae and broadening of terminal loops, or separation of the loops from each other, resulting in paranodal elongation. In freeze-fracture replicas, the E-face of the axolemma showed the normal particle distribution as late as days 3-5. By day 8, however, the nodal particles were patchy and the overall nodal particle density was reduced to approximately half normal. Some normal-looking fibers were present at all stages examined, but their number had declined to about half the total population on day 5 and to less than 10% on day 11. In the rat, the overall sequence of events and time course were comparable to those in the mouse. Thus, the morphological changes found follow approximately the same sequence as that described previously in frog nerves, but progress more rapidly in the mouse and rat.